IMPORTANCE OF 2-O-SULFATE GROUPS OF URONATE RESIDUES IN HEPARIN FOR ACTIVATION OF FGF-1 AND FGF-2

Complete drying of heparin with various concentrations of NaOH by lyop hilization caused specific 2-O-desulfation to various degrees without detectable depolymerization or other chemical changes. In order to ass ess the importance of 2-O-sulfate groups in uronate residues to promot e FGF-1 and FGF-2 activities, various 2-O-desulfated (2-O-DS-) heparin s were quantitatively examined for their effects on FGF-1- and FGF-2-i nduced proliferation of BALB/c3T3 clone A31 (A31) cells and the chlora te-treated cells. Twenty-seven percent or less loss of the 2-O-sulfate groups had no effect on the ability to activate both FGF-1 and FGF-2, while 44% loss resulted in a significant loss of the ability. Complet e loss of the ability was observed in 2-O-DS-heparins with 75% or more 2-O-desulfation. These results suggest that a high content of 2-O-sul fate groups in uronate residues of heparin is required for activation of both FGF-1 and FGF-2.